Skip to main content Accessibility help
×
×
Home

Kainate receptors and signal integration by NG2 glial cells

  • Maria Kukley (a1) and Dirk Dietrich (a1)
Abstract

It is well established that NG2 cells throughout the young and adult brain consistently detect the release of single vesicles filled with glutamate from nearby axons. The released neurotransmitter glutamate electrically excites NG2 cells via non-NMDA (N-methyl-D-aspartic acid) glutamate receptors but the individual contribution of AMPA and kainate receptors to neuron-NG2 cell signalling, is not well understood. Here we pharmacologically block AMPA-type glutamate receptors and investigate whether hippocampal NG2 cells also express the kainate subtype of glutamate receptors and what may be their contribution to synaptic connectivity. It has been shown previously that vesicular glutamate release does not lead to a detectable activation of kainate receptors on NG2 cells. Here we report that while bath application of 250 nM–1 μM kainate does not have a major effect on NG2 cells it consistently induces a small and persistent depolarising current. This current was not mimicked by ATPA, suggesting that this current is carried by non-GluR5 containing kainate receptors. In addition to this inward current, nanomolar concentrations of kainate also produced a dramatic increase in the frequency of spontaneous GABA-A receptor-mediated synaptic currents (IPSCs) in NG2 cells. This increase in spontaneous IPSC frequency was even more pronounced on application of the GluR5-specific agonist ATPA (approximately 15-fold increase in frequency). In contrast, mono-synaptic stimulated IPSCs recorded in NG2 cells were unaffected by kainate receptor activation. Those and further experiments show that the occurrence of the high frequency of IPSCs is due to action potential firing of hippocampal interneurons caused by activation of GluR5 receptors on the somatodendritic membrane of the interneurons. Our data suggest that hippocampal kainate receptors are not only important for communication between neurons but may also play a dual and subtype-specific role for neuron–glia signalling: Firstly, extra-synaptic non-GluR5 kainate receptors in the membrane of NG2 cells are ideally suited to instruct NG2 cells on the population activity of local excitatory neurons via ambient glutamate. Secondly, based on the known importance of GluR5 receptors on hippocampal interneurons for the generation of network rhythms and based on our finding that these interneurons heavily project onto NG2 cells, it appears that synaptic activation of interneuronal GluR5 receptors triggers signalling to NG2 cells which transmits the phase and frequency of ongoing network oscillations in the developing hippocampus.

Copyright
Corresponding author
Correspondence should be addressed to: Dirk Dietrich, Department of Neurosurgery, NCH U1 R035, Experimental Neurophysiology University Clinic Bonn, Sigmund-Freud Street 25, D-53105 Bonn, Germany phone: (49) 228 287 1 9224 fax: (49) 228 287 1 1718 email: dirk.dietrich@ukb.uni-bonn.de
References
Hide All
Barres, B.A. and Raff, M.C. (1993) Proliferation of oligodendrocyte precursor cells depends on electrical activity in axons. Nature 361, 258260.
Bergles, D.E., Roberts, J.D., Somogyi, P. and Jahr, C.E. (2000) Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405, 187191.
Bettler, B. and Mulle, C. (1995) Review: neurotransmitter receptors. II. AMPA and kainate receptors. Neuropharmacology 34, 123139.
Castillo, P.E., Malenka, R.C. and Nicoll, R.A. (1997) Kainate receptors mediate a slow postsynaptic current in hippocampal CA3 neurons. Nature 388, 182186.
Chittajallu, R., Aguirre, A. and Gallo, V. (2004) NG2-positive cells in the mouse white and grey matter display distinct physiological properties. Journal of Physiology 561, 109122.
Cobb, S.R., Buhl, E.H., Halasy, K., Paulsen, O. and Somogyi, P. (1995) Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature 378, 7578.
Cossart, R., Epsztein, J., Tyzio, R., Becq, H., Hirsch, J., Ben-Ari, Y. et al. (2002) Quantal release of glutamate generates pure kainate and mixed AMPA/kainate EPSCs in hippocampal neurons. Neuron 35, 147159.
Cossart, R., Esclapez, M., Hirsch, J.C., Bernard, C. and Ben-Ari, Y. (1998) GluR5 kainate receptor activation in interneurons increases tonic inhibition of pyramidal cells. Nature Neuroscience. 1, 470478.
Demerens, C., Stankoff, B., Logak, M., Anglade, P., Allinquant, B., Couraud, F. et al. (1996) Induction of myelination in the central nervous system by electrical activity. Proceedings of the National Academy of Sciences of the U.S.A. 93, 98879892.
Fields, R.D. (2005) Myelination: an overlooked mechanism of synaptic plasticity?. Neuroscientist 11, 528531.
Frerking, M. and Nicoll, R.A. (2000) Synaptic kainate receptors. Current Opinion in Neurobiology 10, 342351.
Frerking, M. and Ohliger-Frerking, P. (2002) AMPA receptors and kainate receptors encode different features of afferent activity. Journal of Neuroscience 22, 74347443.
Gallo, V., Mangin, J.M., Kukley, M. and Dietrich, D. (2008) Synapses on NG2-expressing progenitors in the brain: multiple functions?. Journal of Physiology 586, 37673781.
Gueler, N., Kukley, M. and Dietrich, D. (2007) TBOA-sensitive uptake limits glutamate penetration into brain slices to a few micrometers. Neuroscience Letters 419, 269272.
Huettner, J.E. (2003) Kainate receptors and synaptic transmission. Progress in Neurobiology 70, 387407.
Jane, D.E., Lodge, D. and Collingridge, G.L. (2009) Kainate receptors: pharmacology, function and therapeutic potential. Neuropharmacology 56, 90113.
Karadottir, R., Hamilton, N.B., Bakiri, Y. and Attwell, D. (2008) Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter. Nature Neuroscience 11, 450456.
Kukley, M., Capetillo-Zarate, E. and Dietrich, D. (2007) Vesicular glutamate release from axons in white matter. Nature Neuroscience 10, 311320.
Kukley, M., Kiladze, M., Tognatta, R., Hans, M., Swandulla, D., Schramm, J. et al. (2008) Glial cells are born with synapses. FASEB Journal. 22, 29572969.
Lahtinen, H., Palva, J.M., Sumanen, S., Voipio, J., Kaila, K. and Taira, T. (2002) Postnatal development of rat hippocampal gamma rhythm in vivo. Journal of Neurophysiology 88, 14691474.
Lin, S.C. and Bergles, D.E. (2004) Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor cells in the hippocampus. Nature Neuroscience 7, 2432.
Lin, S.C., Huck, J.H., Roberts, J.D., Macklin, W.B., Somogyi, P. and Bergles, D.E. (2005) Climbing fiber innervation of NG2-expressing glia in the mammalian cerebellum. Neuron 46, 773785.
Liu, Q.S., Xu, Q., Arcuino, G., Kang, J. and Nedergaard, M. (2004) Astrocyte-mediated activation of neuronal kainate receptors. Proceedings of the National Academy of Sciences of the U.S.A. 101, 31723177.
Mangin, J.M., Kunze, A., Chittajallu, R. and Gallo, V. (2008) Satellite NG2 progenitor cells share common glutamatergic inputs with associated interneurons in the mouse dentate gyrus. Journal of Neuroscience 28, 76107623.
Matthias, K., Kirchhoff, F., Seifert, G., Huttmann, K., Matyash, M., Kettenmann, H. et al. (2003) Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus. Journal of Neuroscience 23, 17501758.
Melyan, Z., Wheal, H.V. and Lancaster, B. (2002) Metabotropic-mediated kainate receptor regulation of IsAHP and excitability in pyramidal cells. Neuron 34, 107114.
Mohns, E.J. and Blumberg, M.S. (2008) Synchronous bursts of neuronal activity in the developing hippocampus: modulation by active sleep and association with emerging gamma and theta rhythms. Journal of Neuroscience 28, 1013410144.
Morin, F., Beaulieu, C. and Lacaille, J.C. (1998) Cell-specific alterations in synaptic properties of hippocampal CA1 interneurons after kainate treatment. Journal of Neurophysiology 80, 28362847.
Ni, Y., Malarkey, E.B. and Parpura, V. (2007) Vesicular release of glutamate mediates bidirectional signaling between astrocytes and neurons. Journal of Neurochemistry 103, 12731284.
Paoletti, P. and Neyton, J. (2007) NMDA receptor subunits: function and pharmacology. Current Opinion in Pharmacology 7, 3947.
Perrais, D., Pinheiro, P.S., Jane, D.E. and Mulle, C. (2009) Antagonism of recombinant and native GluK3-containing kainate receptors. Neuropharmacology 56, 131140.
Seifert, G., Rehn, L., Weber, M. and Steinhauser, C. (1997) AMPA receptor subunits expressed by single astrocytes in the juvenile mouse hippocampus. Brain Research. Molecular Brain Research 47, 286294.
Seifert, G. and Steinhauser, C. (1995) Glial cells in the mouse hippocampus express AMPA receptors with an intermediate Ca2+ permeability. European Journal of Neuroscience 7, 18721881.
Takano, T., Kang, J., Jaiswal, J.K., Simon, S.M., Lin, J.H., Yu, Y. et al. (2005) Receptor-mediated glutamate release from volume sensitive channels in astrocytes. Proceedings of the National Academy of Sciences of the U.S.A. 102, 1646616471.
Tzingounis, A.V. and Wadiche, J.I. (2007) Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nature Reviews. Neuroscience 8, 935947.
Vignes, M. and Collingridge, G.L. (1997) The synaptic activation of kainate receptors. Nature 388, 179182.
Wondolowski, J. and Frerking, M. (2009) Subunit-dependent postsynaptic expression of kainate receptors on hippocampal interneurons in area CA1. Journal of Neuroscience 29, 563574.
Ye, Z.C., Wyeth, M.S., Baltan-Tekkok, S. and Ransom, B.R. (2003) Functional hemichannels in astrocytes: a novel mechanism of glutamate release. Journal of Neuroscience 23, 35883596.
Yuan, X., Eisen, A.M., McBain, C.J. and Gallo, V. (1998) A role for glutamate and its receptors in the regulation of oligodendrocyte development in cerebellar tissue slices. Development 125, 29012914.
Zalc, B. and Fields, R.D. (2000) Do action potentials regulate myelination?. Neuroscientist 6, 513.
Zhou, M. and Kimelberg, H.K. (2000) Freshly isolated astrocytes from rat hippocampus show two distinct current patterns and different [K(+)](o) uptake capabilities. Journal of Neurophysiology 84, 27462757.
Ziskin, J.L., Nishiyama, A., Rubio, M., Fukaya, M. and Bergles, D.E. (2007) Vesicular release of glutamate from unmyelinated axons in white matter. Nature Neuroscience 10, 321330.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Neuron Glia Biology
  • ISSN: 1740-925X
  • EISSN: 1741-0533
  • URL: /core/journals/neuron-glia-biology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed